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Biomedical subjects

I Hutton

Publications and source records attributed to I Hutton.

At least 91 records · Page 5Linked to original sources

Chemotherapy of sarcomas of the limbs by regional perfusion.

From 1957 to 1975, 113 patients with sarcoma of the extremities have been treated with chemotherapy by regional perfusion, either alone or as an adjunct to excisional surgery. Perfusion alone in 54 patients was associated with an early response rate of 83%, but only four patients had complete regression of tumor for longer than three months. When perfusion was followed by immediate or delayed excision, better results were obtained. In 49 Stage I patients and in 24 Stage II patients, cumulative survivals of 66% and 59% were obtained at five years and 66% and 51% at 10 years. The procedure has also been useful in saving functional limbs by converting tumors to operability, and in the palliation of pain and ulceration.

Adolescent

Cardiovascular effects of a new inotropic agent, U. K. 14275, in patients with coronary heart disease.

1 The chronotropic and inotropic properties of U.K. 14275, a phosphodiesterase inhibitor were assessed in patients with coronary heart disease. 2 Left ventricular function was assessed in eight patients with acute myocardial infarction using the non-invasive measurement of systolic time intervals. 3 Twelve patients with angina pectoris were studied during diagnostic coronary arteriography. Left ventricular function was assessed using a high fidelity catheter tipped transducer in the left ventricle. 4 In both groups of patients U.K. 14275 infused intravenously in doses of 32, 64, 128 and 256 microgram kg-1 bodyweight min-1 enhanced the contractile state of the left ventricle without altering the heart rate.

Coronary Disease

Influence of frequency of atrial contraction on coronary blood flow and ventricular performance in the conscious dog with myocardial infarction.

The effects of alterations in the frequency of contraction on coronary blood flow and ventricular performance were studied in 12 conscious, unsedated dogs with established myocardial infarction. Total and regional coronary blood flow was measured using radioactive microspheres. The peak increase in flow to the right ventricle was 71% to the infarcted area of the left ventricle was 72% to the non-infarcted area of the left ventricle was 90% and to the ventricular septum was 104%. Despite the generalized increases in regional myocardial blood flow, flow tended to decrease to the subendocardial portion of the infarcted area of the left ventricle. The peak increases in coronary flow and the reduction in flow to the subendocardial portion of the infarcted area occurred at a heart rate of approximately 200/min provided by atrial pacing. Myocardial contractility, as evidenced by peak increases of 16% in maximum LV dP/dt and 12% in dP/dtP, was only enhanced with abrupt incremental changes in heart rate and not with continuous atrial pacing over 15-min periods. Despite the generalized increases in coronary perfusion coronary sinus oxygen content decreased with a widening of the coronary arteriovenous oxygen difference indicating increased myocardial oxygen usage. Thus increasing frequency of contraction in myocardial infarction results in a slight initial but not sustained inotropic effect, a moderate and generalized increase in regional myocardial blood flow, increased myocardial oxygen consumption, and the potential for subendocardial extension of the area of myocardial damage within the infarcted area.

Animals

Comparison of 12-lead and computer-analysed 3 orthogonal lead electocardiogram in coronary artery disease.

The computer-analysed 3 orthogonal lead system ("3-lead ECG") provides a rapid and consistent interpretation of the electrocardiogram. In 102 patients undergoing selective coronary arteriography, the ability of such a system to predict the presence of absence of coronary artery disease and the site of myocardial ischaemia was compared with that of the conventional scalar electrocardiogram interpreted by cardiologists ("12-lead ECG"). Each system predicted the site of myocardial ischaemia with equal accuracy. The 3-lead ECG was a more sensitive index (3-lead ECG sensitivity=77%; 12-lead ECG sensitivity=70%) but less specific (3-lead ECG specificity=74%; 12-lead ECG specificity=78%). In coronary artery disease, the predictive "index of merit" for the 3-lead ECG was 0-51, compared with 0-48 for the 12-lead ECG. These results provide further justification for the routine use of the 3 orthogonal lead electrocardiogram.

Adult

Influence of dobutamine on regional myocardial blood flow and ventricular performance during acute and chronic myocardial ischemia in dogs.

The data from this study document that dobutamine is a powerful inotropic agent in anesthetized dogs with acute myocardial ischemia and in awake, unsedated ones with chronic myocardial infarction. Dobutamine significantly increases heart rate at relatively small doses in anesthetized dogs with acute myocardial ischemia but considerably larger amounts of dobutamine are required to significantly increase heart rate in awake, unsedated dogs with myocardial infarction. Dobutamine also significantly increases regional myocardial blood flow to all areas of the heart at 20mug/kg/min in both anesthetized dogs with acute myocardial ischemia and awake, unsedated ones with myocardial infarction. However, in anesthetized dogs 20mug/kg/min of dobutamine significantly increases epicardial ST-segment elevation during acute myocardial ischemia. Propranolol prevents the inotropic and chronotropic effects of dobutamine in both anesthetized and awake, unsedated dogs. This study suggests that during experimental acute myocardial ischemia dobutamine given at doses that significantly increase heart rate and contractility may increase the extent of myocardial damage. The data also suggest that this agent should be of value in the setting of severe myocardial depression without associated severe coronary artery disease to increase cardiac contractility at doses that do not markedly alter heart rate. The hemodynamic and coronary blood flow effects of dobutamine in patients with and without severe coronary artery disease should be evaluated.

Acute Disease

Changes in regional coronary blood flow with hypertonic mannitol in conscious dogs.

Systemic haemodynamics and regional myocardial blood flow responses to hypertonic mannitol were studied in 10 conscious and 23 anaesthetized dogs. Mannitol infusion significantly increased regional myocardial blood flow in the conscious, intact dogs. Mannitol increased total coronary flow 20% in anasethetized animals compared to 80% in the awake ones. In both groups mannitol exerted a significant positive inotropic effect as evidenced by increases in maximal LV dp/dt and dp/dt/p. These studies have also demonstrated that the intact conscious dog that has not received any sedation has an inner:outer wall left ventricular flow ratio greater than 1-0.

Anesthesia

Influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance in awake, intact dogs with prolonged coronary artery occlusion.

The influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance in awake, intact, unsedated dogs with myocardial infarction resulting from chronic occlusion of the proximal left anterior descending coronary artery was studied. tmannitol given to increase serum osmolality 20 mOsm increased regional myocardial blood flow to that portion of the left ventricle supplied by the occluded left anterior descending coronary artery by 22 +/- 2.8% (1.06 +/- 0.19 to 1.36 +/- 0.23 ml/min with g-1) without changing the inner:outer wall flow ratio. Mannitol also significantly increased regional myocardial blood flow to other areas of the left ventricle and the ventricular septum. Mean aortic pressure, maximal LV dP/dt, LV dP/dt/P, and cardiac output also increased significantly after mannitol. Thus hypertonic mannitol increases regional myocardial blood flow and ventricular performance in the awake, unsedated dog with prolonged occlusion of the proximal left anterior descending coronary artery. The increase in regional myocardial blood flow after mannitol under these circumstances probably is at least in part secondary to the increase in blood pressure and contractility. The increases in regional myocardial blood flow after mannitol in this study are less impressive than those that have been previously reported in the setting of either no myocardial ischaemia or acute myocardial ischaemia; this is probably due to the vasodilatation that chronic myocardial ischaemia itself produces in the canine heart.

Animals

Relation between extent of coronary artery disease and severity of hyperlipoproteinaemia.

Lipoprotein analyses were performed in 133 male patients and were correlated with the coronary arteriographic findings. The prevalence of hyperlipoproteinaemia was significantly higher in those patients with coronary artery disease (P less than 0-02). In addition, the more extensive the degree of coronary artery pathology the higher were the plasma concentrations of total cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol. Hyperlipoproteinaemia was more prevalent in the younger patients with coronary artery disease (P less than 0-02).

Age Factors

Reduced myocardial reflow and increased coronary vascular resistance following prolonged myocardial ischemia in the dog.

Studies were performed to determine whether an alteration in coronary vascular resistance and a reduction in the reflow phenomenon occurred in the blood-perfused, heparinized canine heart after various periods of myocaridal ischemia. Regional myocardial blood flow was measured with radioactive microspheres. Proximal left anterior descending coronary artery blood flow was measured with a periarterial flow transducer. Reduced reflow to the ischemic portion of the left ventricle and increased resistance in the left anterior descending coronary artery were present after 120 minutes of myocardial ischemia. The reduction in reflow was specific to the subendocardium of the ischemic area. Saline and isosorbide dinitrate (Isordi) did not prevent the increase in coronary vascular resistance or the significant reduction in reflow to the subendocardial portion of the ischemic area. Hypertonic mannitol given so as to increase serum osmolality 40 mosmoles/kg prevented the increase in coronary vascular resistance and modified the reduction in the reflow phenomenon to the subendocardial portion of the ischemic area. Thus, both an increase in coronary vascular resistance and a significant reduction in reflow to the subendocardial portion of the ischemic area occur in the canine heart after 120 minutes of myocardial ischemia. Moreover, the increase in coronary vascular resistance can be prevented and the reduction in reflow to the subendocardial portion of the ischemic area can be modified by the administration of hypertonic mannitol.

Animals

The influence of hypertonic mannitol on regional myocardial blood flow during acute and chronic myocardial ischemia in anesthetized and awake intact dogs.

The influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance was studied during acute myocardial ischemia in awake, unsedated and in anesthesized dogs and after myocardial infarction in awake unsedated dogs. Regional myocardial blood flow was measured with radioactive microspheres. Generalized increases in regional myocardial blood flow occurred after mannitol in all of the different animal models studied. The increases in coronary blood flow after mannitol were just as impressive in the nonischemic regions as in the ischemic portion of the left ventricle in all of the different models that were examined in this study. Improvement in regional myocardial blood flow to the ischemic area of the left ventricle after mannitol was associated with a reduction in ST segment elevation during acute myocardial ischemia in anesthetized dogs. The increases in regional myocardial flow after mannitol were also associated with increases in contractility, but the increases in flow appeared to be more impressive than the changes in contractility. The data obtained demonstrate that mannitol increases regional coronary blood flow to both ischemic and nonischemic myocardium in both anesthetized and awake, unsedated, intact dogs with acute and chronic myocardial ischemia and that mannitol reduces ST segment elevation during acute myocardial ischemia in anesthetized dogs. Thus the results suggest that under these circumstances the increases in regional myocardial blood flow after mannitol are of physiological importance in reducing the extent of myocardial injury. Since coronary blood flow increased to nonischemic regions the increases in regional myocardial flow demonstrated in this study after mannitol cannot be entirely explained by the mechanism of reduction in ischemic cell swelling.

Acute Disease

The effects of a new beta-adrenoceptor blocking compound, tolamolol, on haemo-dynamics and myocardial function in man.

1 The effects of tolamolol on haemodynamics and myocardial contractility were investigated in two groups of six patients undergoing diagnostic cardiac catheterization.2 The intravenous administration of tolamolol (0.15 mg/kg) produced a significant fall in heart rate from a control value (87 +/- 7 to 62 +/- 3 beats/min) 5 min after administration and a concomitant fall in cardiac output from 4.7 +/- 0.9 to 3.5 +/- 0.8 litres/minute. There was no significant change in systemic blood pressure, pulmonary artery blood pressure or stroke volume.3 There was no change in left ventricular end diastolic pressure after tolamolol. There was a fall in the maximum rate of rise of the left ventricular pressure (LV dp/dt(max)) and the derived index of the left ventricular contractile state (V(max)).4 These results suggest that tolamolol has a predominantly negative chronotropic but also a lesser negative inotropic action on the heart.

Adrenergic beta-Antagonists